Dexamethasone inhibits the anti-tumor effect of interleukin 4 on rat experimental gliomas

• Published in: Gene therapy Vol. 10; no. 2; pp. 188 - 192
• Main Authors: BENEDETTI, S, PIROLA, B, POLIANI, P. L, CAJOLA, L, POLLO, B, BAGNATI, R, MAGRASSI, L, TUNICI, P, FINOCCHIARO, G
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.01.2003
• Subjects: Animals; Antineoplastic Agents, Hormonal - pharmacology; Biological and medical sciences; Brain Neoplasms - immunology; Brain Neoplasms - therapy; Contraindications; Dexamethasone - pharmacology; Drug Implants; General pharmacology; Genetic Vectors - administration & dosage; Gliosarcoma - immunology; Gliosarcoma - therapy; Interleukin-4 - genetics; Interleukin-4 - immunology; Medical sciences; Neoplasms, Experimental - immunology; Neoplasms, Experimental - therapy; Neurology; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Rats; Rats, Inbred F344; Retroviridae - genetics; Tumors of the nervous system. Phacomatoses; Vertebrata; Interleukin 4; Mammalia; Dexamethasone; Glioma; Rat; lL-4; Rodentia; Tumor; Experimental study
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3301863

Retroviral-mediated gene transfer of the IL-4 gene into experimental gliomas can cause tumor rejection, supporting the clinical use of this form of gene therapy for glioblastomas (GBM). In a clinical setting, the administration of dexamethasone (dex) is a standard procedure for GBM patients. This led us to examine the effects of dex on IL-4 gene therapy. We injected intracranially Fischer 344 rats with phosphate-buffered saline, 9L gliosarcoma cells mixed with E86.L4SN(200) cells (retroviral producer cells, RPC, transducing IL-4 cDNA) and 9L cells mixed with PA317.STK.SBA cells (control RPC expressing the HSV-tk gene). The rats from each group were treated with 0, 50, 100 or 250 microg dex/kg/day released by osmotic pumps implanted subcutaneously. While 80-100% of rats receiving 9L cells mixed with IL-4 RPC and not treated by dex survived for at least 2 months following tumor injection, only 50% and 17% of rats receiving 50 or 100 microg/kg/day of dex, respectively, reached this time point. These results indicate that dex significantly diminished the anti-tumor effect of IL-4. Thus, in a clinical setting, IL-4 gene transfer should be performed when low levels of dex are administered or in the absence of dex.